^(125)I粒子抑制中分化结肠腺癌的实验研究

Experimental Study about Inhibitory Effect of Iodine-125 on Moderately Differentiated Adenocarcinoma of Colon

目的建立人中分化结肠腺癌细胞裸鼠皮下移植瘤模型,以探讨碘-125(125I)粒子治疗中分化结肠腺癌的有效性。方法将人中分化结肠腺癌细胞(SW480)种植到雄性BALB/c-nu/nu裸小鼠皮下,建立动物模型,用随机抽签法随机将荷瘤裸小鼠分成对照组和实验组(每组24只),对照组植入1颗空白粒子,实验组植入1颗剂量为1.48×107Bq的125I粒子,观察粒子植入后瘤体生长情况,分别于植入后第7、14、21及28天处死实验组与对照组荷瘤裸小鼠,每个时相6只裸小鼠。剥取瘤体,分别用于免疫组化SP法测定增殖细胞核抗原(PCNA)的表达,原位末端标记(TUNEL)法检测肿瘤细胞凋亡情况。结果随着放射时间的延长,从第10天起实验组肿瘤体积明显小于对照组(P<0.05),从第14天开始PCNA标记指数表达显著低于对照组(P<0.05),从第21天开始凋亡指数显著高于对照组(P<0.05)。结论 125I粒子通过持续低剂量辐射后可以下调PCNA的表达,诱导人中分化结肠腺癌细胞凋亡增加,是其抑制人中分化结肠腺癌增殖可能的生物学机理之一。

Objective To approach the inhibitory effect of Iodine-125（125I） on moderately differentiated adenocarcinoma of colon by establishing the nude mice model bearing subcutaneous tumor of SW480 cell.Methods The moderately differentiated adenocarcinoma of colon cells（SW480） were implanted subcutaneously to the nude mice.The bearing tumor nude mice were randomly divided into study group（n=24） and control group（n=24） by using method of random sampling.One blank particle was implanted into the mouse of the control group,a 1.48×107 Bq dosage 125I particle was implanted into the mouse of the study group,then the growth of tumor was observed after implantation.Six bearing tumor nude mice were sacrificed and the tumors were obtained on day 7,14,21,and 28 after implantation,respectively.The expression of proliferating cell nuclear antigen（PCNA） was detected by immunohistochemistry SP method.The cell apoptosis was determined by TUNEL method.Results As the accumulation of radiation time,the volume of tumor in the study group was smaller than that in the control group on day 10 after implantation（P0.05）.The PCNA labeling index in the study group was lower than that in the control group on day 14 after implantation（P0.05）.The apoptotic index in the study group was higher than that in the control group on day 21 after implantation（P0.05）.Conclusion Persistent low dose 125I radiation could down-regulate the expression of PCNA,and induce the apoptosis of moderately differentiated adenocarcinoma of colon cell,which might be a mechanism of inhibiting the proliferation of moderately differentiated adenocarcinoma of colon.